Affinage

ZMYM2

Zinc finger MYM-type protein 2 · UniProt Q9UBW7

Length
1377 aa
Mass
154.9 kDa
Annotated
2026-04-28
100 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ZMYM2 is a nuclear MYM-type zinc-finger protein that functions as a transcriptional corepressor by stabilizing the LSD1-CoREST-HDAC1 complex on chromatin through multivalent SUMO-interacting motifs (SIMs) embedded in its MYM zinc fingers, thereby repressing germline genes, endogenous retroviruses (MERVL), and LINE-1 elements in coordination with PRC1.6 and TRIM28 complexes (PMID:18806873, PMID:32032525, PMID:37395395). ZMYM2 is also recruited to DNA double-strand breaks in a PIAS4/SUMO-dependent manner, where it restricts 53BP1 accumulation to promote BRCA1 loading and homologous recombination (PMID:35253893). Its stability is regulated by PLK1-mediated phosphorylation and HOTAIR-enhanced ubiquitination leading to proteasomal degradation, and it can be pharmacologically degraded via cereblon-dependent ubiquitination by avadomide (PMID:25855382, PMID:34027417). Loss-of-function mutations in ZMYM2 cause congenital anomalies of the kidney and urinary tract (CAKUT), and the t(8;13) translocation fusing its N-terminal dimerization domains to FGFR1 produces a constitutively active cytoplasmic kinase that drives myeloproliferative disease through STAT5, AKT/MAPK, PLCγ1, and Notch signaling (PMID:32891193, PMID:9425908, PMID:15050920).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 High

    Identification of ZMYM2 as a fusion partner of FGFR1 in the t(8;13) translocation established the gene's relevance to myeloproliferative disease and revealed that its MYM zinc-finger domains mediate homodimerization, constitutive kinase activation, and cytoplasmic relocalization of the fusion protein.

    Evidence Molecular cloning, cDNA sequencing, in vitro kinase assay, deletion mapping, and subcellular fractionation in transfected cells

    PMID:9425908 PMID:9576949

    Open questions at the time
    • Normal cellular function of wild-type ZMYM2 was unknown
    • Mechanism of kinase activation beyond dimerization was not resolved
    • No in vivo disease model yet established
  2. 2000 High

    Mapping the self-association domain to the proline-rich region of ZMYM2 demonstrated that this region alone is sufficient for oligomerization and transformation, separating it from the zinc-finger domains initially thought to drive dimerization.

    Evidence Domain-swap constructs fused to FGFR1 intracellular domain tested in Ba/F3 transformation and co-immunoprecipitation

    PMID:10887137 PMID:10935490

    Open questions at the time
    • Structural basis for proline-rich domain oligomerization not determined
    • Downstream signaling pathways not yet dissected
  3. 2004 High

    In vivo modeling of ZMYM2-FGFR1 in murine bone marrow transplantation recapitulated human EMS-like myeloproliferative disease with T lymphoma, and Y766F mutagenesis identified PLCγ1 as a critical downstream effector of the fusion kinase.

    Evidence Murine bone marrow transplantation with site-directed FGFR1 mutants and disease phenotyping

    PMID:15050920

    Open questions at the time
    • Relative contributions of STAT5 vs. PLCγ1 vs. other pathways not fully delineated
    • Role of Notch activation not yet recognized
  4. 2007 Medium

    Dissection of ZMYM2-FGFR1 downstream signaling showed that the fusion kinase activates both AKT and MAPK pathways to phosphorylate FOXO3a and BAD, which are sequestered by 14-3-3 proteins, while STAT5 was shown to be essential for anti-apoptotic signaling and BclXL upregulation.

    Evidence Phospho-specific Western blots, 14-3-3 antagonist peptide R18, dominant-negative STAT mutants, apoptosis assays

    PMID:14660670 PMID:17389761

    Open questions at the time
    • Direct kinase-substrate relationships for AKT/MAPK activation not established
    • Therapeutic targeting of these pathways not tested in vivo
  5. 2008 High

    The first insight into wild-type ZMYM2 function came from the discovery that it preferentially binds the intact LSD1-CoREST-HDAC1 ternary complex (not individual subunits) through its MYM zinc fingers, associates with chromatin independently of this complex, and represses E-cadherin, establishing ZMYM2 as a transcriptional corepressor.

    Evidence Co-immunoprecipitation, in vitro SUMOylation assay, chromatin immunoprecipitation, domain mapping

    PMID:18806873

    Open questions at the time
    • Genome-wide target genes were unknown
    • Whether SUMO-dependent binding is the sole recruitment mechanism was unclear
  6. 2011 Medium

    Notch1 was identified as a constitutively activated pathway in ZMYM2-FGFR1-driven T-cell lymphomas, and pharmacologic or genetic Notch inhibition delayed tumorigenesis, revealing an additional oncogenic signaling axis.

    Evidence Murine ZMYM2-FGFR1 lymphoma model with γ-secretase inhibitor treatment and shRNA knockdown of Notch pathway components

    PMID:21527531

    Open questions at the time
    • Whether Notch activation is direct or indirect remains unclear
    • Interaction between Notch and STAT5/PLCγ1 pathways not resolved
  7. 2014 Medium

    The MYM-type zinc fingers were biochemically defined as bona fide SUMO-interacting motifs that bind the same SUMO-2 surface as canonical SIMs and are necessary for PML nuclear body localization, unifying ZMYM2's chromatin association mechanism with its subnuclear targeting.

    Evidence Binding assays with truncation/domain mutagenesis and immunofluorescence for PML body localization

    PMID:17027752 PMID:25133527

    Open questions at the time
    • Structural resolution of the MYM-SUMO interface was lacking
    • Whether all MYM fingers have equivalent SUMO affinity was not resolved
  8. 2015 High

    ZMYM2 protein stability was shown to be controlled by PLK1-mediated phosphorylation leading to HOTAIR-enhanced ubiquitination and proteasomal degradation, with ZMYM2 loss causing global histone modification changes due to destabilization of the LSD1/CoREST/HDAC1 complex; separately, multi-SUMO binding through multiple SIMs was confirmed as required for chromatin recruitment.

    Evidence Phosphorylation mapping, ubiquitination assays, HOTAIR overexpression, histone modification ChIP, multi-SUMO binding screen with SIM mutagenesis

    PMID:25855382 PMID:26283374

    Open questions at the time
    • Identity of the E3 ligase mediating PLK1-triggered degradation not determined
    • Whether HOTAIR regulation is tissue-specific was unknown
  9. 2020 High

    ZMYM2 was established as essential for silencing MERVL elements via LSD1/HDAC recruitment, for restricting pluripotency gene expression in human ESCs through the LSD-CoREST and BHC complexes, and for the totipotency-to-pluripotency transition during early embryonic development.

    Evidence CRISPR screens in ESCs, ZMYM2-knockout ESC generation, ChIP-seq, RNA-seq, teratoma assays, embryo microinjection

    PMID:32032525 PMID:32559458

    Open questions at the time
    • Mechanism distinguishing ZMYM2 targets from other CoREST complex targets not resolved
    • In vivo embryonic requirement characterized only in mouse
  10. 2020 High

    Loss-of-function ZMYM2 mutations were identified as a cause of congenital anomalies of the kidney and urinary tract (CAKUT), with ZMYM2 interacting with FOXP1 and heterozygous Zmym2-deficient mice recapitulating renal malformations, linking the gene's corepressor function to organogenesis.

    Evidence Whole-exome sequencing of CAKUT families, protein-protein interaction assays, Xenopus morpholino knockdown, heterozygous mouse knockout

    PMID:32891193

    Open questions at the time
    • Specific transcriptional targets relevant to kidney development not identified
    • Whether FOXP1 interaction is direct or complex-mediated not resolved
  11. 2021 High

    The cereblon-modulating drug avadomide was shown to induce CRBN-dependent ubiquitination and degradation of ZMYM2 through its N-terminal MYM domain, providing a pharmacologic strategy to degrade both wild-type ZMYM2 and oncogenic ZMYM2-FGFR1/FLT3 fusion proteins.

    Evidence Proteomics, CRBN co-immunoprecipitation, ubiquitination assay, domain mapping, mouse xenograft in vivo degradation

    PMID:34027417

    Open questions at the time
    • Clinical efficacy in patients with ZMYM2-FGFR1 fusions not yet demonstrated
    • Selectivity across other MYM-domain proteins not fully characterized
  12. 2022 High

    ZMYM2 was found to be recruited to DNA double-strand breaks in a PIAS4- and SUMO-dependent manner, where it suppresses 53BP1 loading to favor BRCA1 and homologous recombination, establishing a direct role in DNA damage repair pathway choice.

    Evidence siRNA epistasis (53BP1 depletion rescue), PARP inhibitor and ionizing radiation sensitivity assays, immunofluorescence for DSB repair factor recruitment

    PMID:35253893

    Open questions at the time
    • Biochemical mechanism by which ZMYM2 displaces or prevents 53BP1 binding not determined
    • Whether LSD1/CoREST complex participates in the DSB function of ZMYM2 unknown
  13. 2023 High

    ZMYM2 was shown to be essential for DNA methylation at germline gene promoters and active LINE-1 elements during embryonic development by localizing to PRC1.6 and TRIM28 binding sites and facilitating H3K4 demethylation to create a chromatin state permissive for de novo DNA methylation.

    Evidence Zmym2-knockout mice (embryonic lethal by E10.5), bisulfite sequencing, ChIP-seq for H3K4me, RNA-seq in mouse and human ESCs

    PMID:37395395

    Open questions at the time
    • Whether ZMYM2 directly recruits DNMT3A/B or acts only through H3K4 demethylation not distinguished
    • Relationship between LINE-1 derepression and embryonic lethality not causally established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of the multivalent MYM-SUMO interaction, how ZMYM2 is differentially partitioned between transcriptional repression and DNA repair functions, and whether its role in DNA methylation establishment is mechanistically separable from its LSD1-CoREST complex-stabilizing activity.
  • No high-resolution structure of ZMYM2 or its MYM-SUMO complexes exists
  • Whether ZMYM2's DSB repair and transcriptional repression functions share a common SUMO-dependent mechanism is untested
  • Tissue-specific roles beyond kidney and germline are poorly characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0098772 molecular function regulator activity 3 GO:0042393 histone binding 2
Localization
GO:0005634 nucleus 5 GO:0005694 chromosome 3 GO:0005730 nucleolus 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-73894 DNA Repair 1
Partners
CORESTFGFR1FOXP1HDAC1LSD1PIAS4PMLTRIM28
Complex memberships
LSD1-CoREST-HDAC1 (LCH/BHC)PRC1.6

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 ZMYM2 (ZNF198) is fused to FGFR1 via the t(8;13)(p11;q11-12) translocation; the ZNF198-FGFR1 fusion protein contains ZNF198 zinc-finger (MYM) domains linked to the FGFR1 tyrosine-kinase domain, localizes predominantly to the cytoplasm, and transient expression directs synthesis of an ~87-kD polypeptide with ZNF198 zinc-finger-mediated homodimerization proposed as the activation mechanism. Molecular cloning, cDNA sequencing, transient expression in cells, subcellular localization Nature genetics High 9425908
1998 The FIM/FGFR1 (ZMYM2-FGFR1) fusion protein has constitutive tyrosine kinase activity, established by in vitro kinase assay; wild-type FIM (ZMYM2) has nuclear and nucleolar localization dependent on its C-terminal region, which is lost in the cytoplasmic fusion protein. In vitro kinase assay, subcellular fractionation/immunofluorescence, deletion mapping Proceedings of the National Academy of Sciences of the United States of America High 9576949
1999 ZNF198-FGFR1 is a cytoplasmic protein that self-associates (as shown by co-immunoprecipitation of differentially tagged in vitro translated products) and has constitutive transformation activity, converting Ba/F3 cells to IL-3 independence; STAT1 and STAT5 are constitutively tyrosine-phosphorylated in transformed cells. Co-immunoprecipitation, Ba/F3 transformation assay, Western blot for phospho-STATs Neoplasia High 10935490
1999 FIM (ZMYM2) localizes to the nucleus and nucleolus (colocalizing with upstream binding factor), indicating a potential role in rRNA transcription regulation; targeting to the nucleus depends on the C-terminal region absent in FIM-FGFR1; FIM-FGFR1 has constitutive dimerization capability mediated by the FIM N-terminal sequences and promotes Ba/F3 cell survival after IL-3 withdrawal. Confocal immunofluorescence, subcellular fractionation, deletion mapping, Ba/F3 survival assay The Journal of biological chemistry High 10480903
2000 The ZNF198 proline-rich region constitutes a novel self-association (oligomerization) domain; when fused to the intracellular domain of FGFR1, this proline-rich region is sufficient to cause oligomerization, FGFR1 tyrosine kinase activation, and transformation of Ba/F3 cells to IL-3 independence. Deletion/domain-swap constructs, co-immunoprecipitation, Ba/F3 transformation assay, kinase activity assay Blood High 10887137
2003 ZNF198 forms protein complexes with DNA repair proteins HHR6A/6B (RAD6 homologs) and RAD18 as identified by yeast two-hybrid and confirmed by co-immunoprecipitation; the ZNF198-FGFR1 fusion also binds HHR6 but not RAD18; cells expressing the fusion kinase show markedly increased sensitivity to UVB irradiation, suggesting dominant-negative interference with DNA repair. Yeast two-hybrid, co-immunoprecipitation, UVB sensitivity assay Oncogene Medium 12776193
2003 STAT5 activation is essential for the anti-apoptotic effect of ZNF198-FGFR1, for elevated BclXL levels, cell cycle progression under cytokine deprivation, and upregulation of DNA repair protein Rad51; demonstrated using dominant-negative STAT mutants. Dominant-negative STAT mutant induction, cell viability assays, Western blot The Journal of biological chemistry Medium 14660670
2004 ZNF198-FGFR1 induces EMS-like myeloproliferative disease with T lymphoma in mice; mutation of FGFR1 Tyr766 attenuates both myeloid and lymphoid diseases, identifying phospholipase C-gamma1 as a downstream effector of the fusion kinase. Murine bone marrow transplantation model, site-directed mutagenesis (Y766F), disease phenotyping Cancer cell High 15050920
2005 ZNF198 interacts with splicing-associated proteins PSF, hnRNP H3, hnRNP A2/B1, and TLS/FUS, as identified by immunoprecipitation of GFP-tagged ZNF198 combined with MALDI-TOF mass spectrometry and confirmed by Western blotting; ZNF198-FGFR1 fusion protein does not bind PSF or PTB due to differential cytoplasmic localization. Co-immunoprecipitation with GFP tag, MALDI-TOF mass spectrometry, Western blot confirmation Experimental cell research Medium 15975576
2006 ZNF198 localizes to PML nuclear bodies and interacts with SUMO-1 and PML; ZNF198 is covalently modified (sumoylated) by SUMO-1; mutation of the SUMO-1 binding site in ZNF198 results in loss of distinct PML bodies and reduced PML levels; the ZNF198-FGFR1 fusion (lacking the SUMO-1 binding site) causes preferential cytoplasmic SUMO-1 localization associated with loss of PML bodies. Yeast two-hybrid, co-immunoprecipitation, confocal immunofluorescence, SUMO binding-site mutagenesis Experimental cell research Medium 17027752
2007 ZNF198-FGFR1 activates both AKT and MAPK prosurvival signaling pathways, resulting in phosphorylation of FOXO3a at T32 and BAD at S112, which are sequestered by 14-3-3 to prevent apoptosis; disruption of 14-3-3-ligand association induces apoptosis in ZNF198-FGFR1-transformed cells, operating through liberation of FOXO3a. Western blot for phospho-proteins, peptide-based 14-3-3 antagonist (R18), apoptosis assays Blood Medium 17389761
2008 ZNF198 binds preferentially to the intact LSD1-CoREST-HDAC1 (LCH) ternary complex but not to individual subunits; ZNF198 and REST binding to LCH are mutually exclusive; ZNF198 associates with chromatin independently of LCH; SUMO modification of HDAC1 weakens its interaction with CoREST but stimulates binding to ZNF198; ZNF198-like proteins are required for repression of E-cadherin but not REST-responsive genes; LCH- and HDAC1-SUMO-binding domains were mapped to tandem MYM-type zinc fingers. Co-immunoprecipitation, chromatin immunoprecipitation, in vitro SUMOylation assay, domain mapping PloS one High 18806873
2009 ZNF198-FGFR1 fusion kinase specifically phosphorylates SSBP2 and ABL proteins (among others including FLJ14235, CALM, TRIM4) as identified by anti-phosphotyrosine immunoprecipitation and mass spectrometry, confirmed by protein-specific immunoprecipitation and Western blotting; phosphorylation sites within the ZNF198 moiety of the chimeric protein were also identified. Anti-phosphotyrosine immunoprecipitation, MALDI-TOF/MS, protein-specific immunoprecipitation and Western blot Proteomics Medium 19658100
2011 ZMYM2-FGFR1 fusion kinase induces constitutive activation of Notch1 and its downstream target genes in T-cell lymphomas; pharmacologic inhibition of Notch signaling with γ-secretase inhibitors or shRNA targeting of Notch1/CBF1/MAML1 significantly delayed or inhibited tumorigenesis in vivo; constitutive Notch1 activation is due to 5' promoter deletions and alternative promoter usage. Murine ZMYM2-FGFR1 lymphoma model, pharmacologic inhibition, shRNA knockdown, in vivo tumor studies, promoter sequencing Blood Medium 21527531
2011 ZNF198 protein levels are reduced by Plk1-mediated phosphorylation in HBV-infected hepatocytes; the Polo-box domain of Plk1 co-immunoprecipitates with ZNF198 and SUZ12, identifying them as Plk1 substrates; siRNA knockdown of ZNF198 reduces p53 stability and DNA repair, rescues pX-expressing hepatocytes from DNA damage-induced apoptosis, and increases pX-induced polyploidy and oncogenic transformation. Co-immunoprecipitation, siRNA knockdown, Western blot, apoptosis and DNA repair assays Hepatology Medium 21480320
2014 MYM-type zinc fingers of ZNF198 (and ZNF261) are necessary and sufficient for SUMO-2 binding and function as SUMO-interacting motifs (SIMs); individual MYM-type zinc fingers interact with the same surface on SUMO-2 as the archetypal consensus SIM; zinc is contained in these fingers but is not required for SUMO binding; MYM-type zinc fingers of ZNF198 are necessary for localization to PML nuclear bodies. Binding assays, truncation/domain mutagenesis, immunofluorescence microscopy PloS one Medium 25133527
2015 PLK1 induces proteasomal degradation of ZNF198 by site-specific phosphorylation; PLK1-dependent ubiquitination of ZNF198 is enhanced by the lncRNA HOTAIR, significantly reducing ZNF198 stability; ZNF198 stabilizes the LSD1/CoREST/HDAC1 complex and its degradation leads to global changes in histone modifications. Site-specific phosphorylation mapping, ubiquitination assays, HOTAIR expression, Western blot for protein stability, histone modification ChIP Cancer research High 25855382
2015 ZMYM2's multi-SUMO-binding activity (through multiple SIM modules in its MYM-type zinc fingers) is required for its recruitment to chromatin; identified through a screen for multi-SUMO-binding proteins. Multi-SUMO binding screen, SIM mutagenesis, chromatin recruitment assays Proceedings of the National Academy of Sciences of the United States of America High 26283374
2020 ZMYM2 recruits the LSD1/HDAC corepressor complex to MERVL LTRs for transcriptional repression; miR-344 (activated by DUX) post-transcriptionally represses ZMYM2 and LSD1, relieving MERVL repression and inducing 2C-like state; zygotic depletion of Zmym2 compromises totipotency-to-pluripotency transition during early development. miRNA overexpression, ZMYM2 knockdown, ChIP, RNA-seq, embryo microinjection Cell stem cell High 32032525
2020 ZMYM2 loss-of-function mutations cause congenital anomalies of the kidney and urinary tract (CAKUT); ZMYM2 protein interacts with FOXP1 (a transcription factor linked to CAKUT) and additional epigenetic silencing complexes as shown by protein-protein interaction assays; heterozygous Zmym2-deficient mice recapitulate CAKUT features with high penetrance. Whole-exome sequencing, protein-protein interaction assays, Xenopus morpholino knockdown, heterozygous mouse knockout American journal of human genetics High 32891193
2020 ZMYM2 is essential for human ESC growth restriction; ZMYM2-null ESCs overexpress pluripotency genes and show genome-wide promoter-localized histone H3 hyper-acetylation; ZMYM2 acts as a component of LSD-CoREST and BHC repressive complexes to restrict pluripotency gene expression; ZMYM2-null cells fail to differentiate and cannot produce teratomas. CRISPR-based genetic screen in 703 chromatin genes, knockout ESC generation, RNA-seq, ChIP-seq for H3 acetylation, differentiation and teratoma assays Stem cell reports High 32559458
2021 Avadomide (CC-122) induces CRBN-dependent ubiquitination and proteasomal degradation of ZMYM2; the minimal drug-responsive element is a zinc-chelating MYM domain contained in the N-terminal portion universally present in ZMYM2-FGFR1 and ZMYM2-FLT3 fusion proteins; avadomide degrades both chimeric oncoproteins in vitro and in vivo. Proteomics, CRBN co-immunoprecipitation, ubiquitination assay, domain mapping, mouse xenograft in vivo degradation Blood cancer discovery High 34027417
2022 ZMYM2 is recruited to DNA double-strand breaks and suppresses 53BP1 loading to favor BRCA1 recruitment and homologous recombination (HR); ZMYM2 recruitment and 53BP1 suppression requires SUMO E3 ligase PIAS4 and SUMO binding by ZMYM2; ZMYM2-deficient cells display genome instability, PARP inhibitor sensitivity, ionizing radiation sensitivity, and reduced HR; depletion of 53BP1 in ZMYM2-deficient cells rescues BRCA1 recruitment and HR. siRNA knockdown, epistasis (53BP1 depletion rescue), PARP inhibitor/IR sensitivity assays, immunofluorescence for DSB marker recruitment, PIAS4 requirement Nucleic acids research High 35253893
2023 ZMYM2 is essential for DNA methylation of germline gene promoters and active LINE-1 elements during embryonic development; Zmym2-/- mice show embryonic lethality by E10.5; ZMYM2 localizes to PRC1.6 and TRIM28 complex binding sites, mediating repression of germline genes and transposons respectively; absence of ZMYM2 causes hypermethylation of histone H3K4 at target sites, creating a chromatin landscape unfavorable for DNA methylation establishment; ZMYM2-/- human ESCs show aberrant upregulation of young LINE elements. Zmym2 knockout mice, bisulfite sequencing (DNA methylation), ChIP-seq, RNA-seq, H3K4me analysis, human ESC knockout Nucleic acids research High 37395395

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1986 Two regulatory fim genes, fimB and fimE, control the phase variation of type 1 fimbriae in Escherichia coli. The EMBO journal 322 2874022
1998 FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome. Nature genetics 261 9425908
2012 Essential features and rational design of CRISPR RNAs that function with the Cas RAMP module complex to cleave RNAs. Molecular cell 225 22227116
1987 Three fim genes required for the regulation of length and mediation of adhesion of Escherichia coli type 1 fimbriae. Molecular & general genetics : MGG 206 2890081
1998 Consistent fusion of ZNF198 to the fibroblast growth factor receptor-1 in the t(8;13)(p11;q12) myeloproliferative syndrome. Blood 143 9716603
1996 Interaction of FimB and FimE with the fim switch that controls the phase variation of type 1 fimbriae in Escherichia coli K-12. Molecular microbiology 134 8878036
1998 Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13). Proceedings of the National Academy of Sciences of the United States of America 133 9576949
2004 Distinct stem cell myeloproliferative/T lymphoma syndromes induced by ZNF198-FGFR1 and BCR-FGFR1 fusion genes from 8p11 translocations. Cancer cell 130 15050920
2019 A short translational ramp determines the efficiency of protein synthesis. Nature communications 129 31852903
2018 Quantitative and Qualitative Assessment of the Posterior Medial Meniscus Anatomy: Defining Meniscal Ramp Lesions. The American journal of sports medicine 126 30525875
2015 PLK1 and HOTAIR Accelerate Proteasomal Degradation of SUZ12 and ZNF198 during Hepatitis B Virus-Induced Liver Carcinogenesis. Cancer research 118 25855382
2020 DUX-miR-344-ZMYM2-Mediated Activation of MERVL LTRs Induces a Totipotent 2C-like State. Cell stem cell 109 32032525
2011 Past and present issues in Rasch analysis: the functional independence measure (FIM™) revisited. Journal of rehabilitation medicine 103 21947180
1987 Identification of two ancillary subunits of Escherichia coli type 1 fimbriae by using antibodies against synthetic oligopeptides of fim gene products. Journal of bacteriology 100 2890622
2005 Probing the mechanical folding kinetics of TAR RNA by hopping, force-jump, and force-ramp methods. Biophysical journal 93 16214869
2006 Upregulation of persistent and ramp sodium current in dorsal horn neurons after spinal cord injury. Experimental brain research 84 16718433
2011 Regulation of fim genes in uropathogenic Escherichia coli. World journal of clinical infectious diseases 82 23638406
1994 The leucine-responsive regulatory protein binds to the fim switch to control phase variation of type 1 fimbrial expression in Escherichia coli K-12. Journal of bacteriology 82 7916011
2009 High specific infectivity of plasma virus from the pre-ramp-up and ramp-up stages of acute simian immunodeficiency virus infection. Journal of virology 78 19129448
2004 Cartilage injury by ramp compression near the gel diffusion rate. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 77 14656673
1994 Mutational analysis of the Bordetella pertussis fim/fha gene cluster: identification of a gene with sequence similarities to haemolysin accessory genes involved in export of FHA. Molecular microbiology 75 8170396
2012 Targeting a family B GPCR/RAMP receptor complex: CGRP receptor antagonists and migraine. British journal of pharmacology 74 21871019
2001 Stamina pistilloida, the Pea ortholog of Fim and UFO, is required for normal development of flowers, inflorescences, and leaves. The Plant cell 74 11158527
2011 Resolution-associated molecular patterns (RAMP): RAMParts defending immunological homeostasis? Clinical and experimental immunology 72 21671907
2008 ZNF198 stabilizes the LSD1-CoREST-HDAC1 complex on chromatin through its MYM-type zinc fingers. PloS one 72 18806873
1989 Retroviral insertions in the CB-1/Fim-3 common site of integration activate expression of the Evi-1 gene. Oncogene 70 2542863
2011 Structural insights into RAMP modification of secretin family G protein-coupled receptors: implications for drug development. Trends in pharmacological sciences 66 21722971
2008 Optical monitoring of neuronal activity at high frame rate with a digital random-access multiphoton (RAMP) microscope. Journal of neuroscience methods 66 18634822
2019 Multiplexed analysis of the secretin-like GPCR-RAMP interactome. Science advances 65 31555726
2000 ZNF198-FGFR1 transforming activity depends on a novel proline-rich ZNF198 oligomerization domain. Blood 62 10887137
1999 Characterization of FIM-FGFR1, the fusion product of the myeloproliferative disorder-associated t(8;13) translocation. The Journal of biological chemistry 59 10480903
2006 A tightly regulated inducible expression system utilizing the fim inversion recombination switch. Biotechnology and bioengineering 58 16534780
2011 Shared and separate functions of the RAMP-based adrenomedullin receptors. Peptides 57 21645567
1999 Construct validity of the functional independence measure (FIM): questioning the unidimensionality of the scale and the "value" of FIM scores. Scandinavian journal of rehabilitation medicine 57 10230001
2009 DNA relaxation-dependent phase biasing of the fim genetic switch in Escherichia coli depends on the interplay of H-NS, IHF and LRP. Molecular microbiology 55 19889099
1986 fim-1 and fim-2: two new integration regions of Friend murine leukemia virus in myeloblastic leukemias. Journal of virology 52 3464762
2011 Proteins ZNF198 and SUZ12 are down-regulated in hepatitis B virus (HBV) X protein-mediated hepatocyte transformation and in HBV replication. Hepatology (Baltimore, Md.) 50 21480320
2007 14-3-3 Integrates prosurvival signals mediated by the AKT and MAPK pathways in ZNF198-FGFR1-transformed hematopoietic cells. Blood 48 17389761
2018 RaMP: A Comprehensive Relational Database of Metabolomics Pathways for Pathway Enrichment Analysis of Genes and Metabolites. Metabolites 45 29470400
2015 Screen for multi-SUMO-binding proteins reveals a multi-SIM-binding mechanism for recruitment of the transcriptional regulator ZMYM2 to chromatin. Proceedings of the National Academy of Sciences of the United States of America 44 26283374
2012 Porphyromonas gingivalis FimA fimbriae: fimbrial assembly by fimA alone in the fim gene cluster and differential antigenicity among fimA genotypes. PloS one 44 22970139
2003 Critical role of STAT5 activation in transformation mediated by ZNF198-FGFR1. The Journal of biological chemistry 44 14660670
1999 ZNF198-FGFR1 transforms Ba/F3 cells to growth factor independence and results in high level tyrosine phosphorylation of STATS 1 and 5. Neoplasia (New York, N.Y.) 44 10935490
2013 Role of CGRP-receptor component protein (RCP) in CLR/RAMP function. Current protein & peptide science 40 23745704
2004 Crystallographic structure of the nuclease domain of 3'hExo, a DEDDh family member, bound to rAMP. Journal of molecular biology 40 15451662
2007 The leucine-responsive regulatory protein, Lrp, activates transcription of the fim operon in Salmonella enterica serovar typhimurium via the fimZ regulatory gene. Journal of bacteriology 39 17981960
2020 Mutations of the Transcriptional Corepressor ZMYM2 Cause Syndromic Urinary Tract Malformations. American journal of human genetics 38 32891193
2023 RaMP-DB 2.0: a renovated knowledgebase for deriving biological and chemical insight from metabolites, proteins, and genes. Bioinformatics (Oxford, England) 37 36373969
2011 Constitutive Notch pathway activation in murine ZMYM2-FGFR1-induced T-cell lymphomas associated with atypical myeloproliferative disease. Blood 36 21527531
1990 Expression of spasmolysin (FIM-A.1): an integumentary mucin from Xenopus laevis. Experimental cell research 36 2196180
2000 Effects of local transcription and H-NS on inversion of the fim switch of Escherichia coli. Molecular microbiology 34 10792731
2015 Detection of pap, sfa, afa, foc, and fim Adhesin-Encoding Operons in Uropathogenic Escherichia coli Isolates Collected From Patients With Urinary Tract Infection. Jundishapur journal of microbiology 33 26464770
2002 Fifteen minutes of fim: control of type 1 pili expression in E. coli. Omics : a journal of integrative biology 33 11881836
2021 Avadomide induces degradation of ZMYM2 fusion oncoproteins in hematologic malignancies. Blood cancer discovery 32 34027417
2018 Population Frequency of Serous Tubal Intraepithelial Carcinoma (STIC) in Clinical Practice Using SEE-Fim Protocol. JNCI cancer spectrum 32 31360879
2014 Bordetella pertussis fimbriae (Fim): relevance for vaccines. Expert review of vaccines 32 25102891
2012 The response of Na(V)1.3 sodium channels to ramp stimuli: multiple components and mechanisms. Journal of neurophysiology 32 23114218
1998 Regulation of type 1 fimbrial expression in uropathogenic Escherichia coli: heterogeneity of expression through sequence changes in the fim switch region. Molecular microbiology 32 9622361
1992 Identification of ancillary fim genes affecting fimA expression in Salmonella typhimurium. Journal of bacteriology 32 1360005
2016 The expanding repertoire of receptor activity modifying protein (RAMP) function. Critical reviews in biochemistry and molecular biology 30 26740457
2014 Characterization of the SUMO-binding activity of the myeloproliferative and mental retardation (MYM)-type zinc fingers in ZNF261 and ZNF198. PloS one 28 25133527
2006 ZNF198, a zinc finger protein rearranged in myeloproliferative disease, localizes to the PML nuclear bodies and interacts with SUMO-1 and PML. Experimental cell research 28 17027752
1999 Desensitization of CGRP and adrenomedullin receptors in SK-N-MC cells: implications for the RAMP hypothesis. Endocrinology 28 9886866
2019 Adult Cardiomyocyte Cell Cycle Detour: Off-ramp to Quiescent Destinations. Trends in endocrinology and metabolism: TEM 27 31262545
1991 A molecular genetic linkage map of mouse chromosome 18, including spm, Grl-1, Fim-2/c-fms, and Mbp. Biochemical genetics 27 1679325
2012 RAMP like proteins : RTP and REEP family of proteins. Advances in experimental medicine and biology 26 22434109
1996 Response of cardiac myocytes to a ramp increase of diacylglycerol generated by photolysis of a novel caged diacylglycerol. Biophysical journal 26 9172772
2019 Reversible association with motor proteins (RAMP): A streptavidin-based method to manipulate organelle positioning. PLoS biology 24 31100061
2013 Positive charge loading at protein termini is due to membrane protein topology, not a translational ramp. Molecular biology and evolution 24 24077849
2006 Induction of the plasminogen activator inhibitor-2 in cells expressing the ZNF198/FGFR1 fusion kinase that is involved in atypical myeloproliferative disease. Blood 24 16410451
1999 Cloning and mapping of members of the MYM family. Genomics 24 10486218
1999 Analysis of the type 1 pilin gene cluster fim in Salmonella: its distinct evolutionary histories in the 5' and 3' regions. Journal of bacteriology 24 9973358
2003 ZNF198 protein, involved in rearrangement in myeloproliferative disease, forms complexes with the DNA repair-associated HHR6A/6B and RAD18 proteins. Oncogene 22 12776193
1991 The frequency of fim genes among Salmonella serovars. Microbial pathogenesis 22 1686630
2023 ZMYM2 is essential for methylation of germline genes and active transposons in embryonic development. Nucleic acids research 21 37395395
2022 ZMYM2 restricts 53BP1 at DNA double-strand breaks to favor BRCA1 loading and homologous recombination. Nucleic acids research 21 35253893
2019 Development of chimeric and bifunctional antagonists for CLR/RAMP receptors. PloS one 21 31150417
1999 The genomic structure of ZNF198 and location of breakpoints in the t(8;13) myeloproliferative syndrome. Genomics 21 9889006
2017 Development of diagnostic SCAR markers for genomic DNA amplifications in breast carcinoma by DNA cloning of high-GC RAMP-PCR fragments. Oncotarget 20 28410206
2006 Risk assessment of patient handling with ambulance stretcher systems (ramp/(winch), easi-loader, tail-lift) using biomechanical failure criteria. Medical engineering & physics 20 17064948
2022 Single agent VS-6766 or VS-6766 plus defactinib in KRAS-mutant non-small-cell lung cancer: the RAMP-202 phase II trial. Future oncology (London, England) 19 35285277
2018 Regulation of cardiovascular development and homeostasis by the adrenomedullin-RAMP system. Peptides 19 29689347
2013 Regulation of adrenomedullin and its family peptide by RAMP system--lessons from genetically engineered mice. Current protein & peptide science 19 23745699
2007 Combined translocation with ZNF198-FGFR1 gene fusion and deletion of potential tumor suppressors in a myeloproliferative disorder. Cancer genetics and cytogenetics 19 17321332
2005 Mass spectroscopy identifies the splicing-associated proteins, PSF, hnRNP H3, hnRNP A2/B1, and TLS/FUS as interacting partners of the ZNF198 protein associated with rearrangement in myeloproliferative disease. Experimental cell research 19 15975576
2013 A ZMYM2-FGFR1 8p11 myeloproliferative neoplasm with a novel nonsense RUNX1 mutation and tumor lysis upon imatinib treatment. Cancer genetics 18 23751892
2012 The mysterious RAMP proteins and their roles in small RNA-based immunity. Protein science : a publication of the Protein Society 18 22323284
2025 Efficacy and Safety of Avutometinib ± Defactinib in Recurrent Low-Grade Serous Ovarian Cancer: Primary Analysis of ENGOT-OV60/GOG-3052/RAMP 201. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 17 40644648
2016 Development of ZMYM2-FGFR1 driven AML in human CD34+ cells in immunocompromised mice. International journal of cancer 17 27005999
2007 Evaluation of ADL in patients with Hunter disease using FIM score. Brain & development 17 17307320
2020 Small and large cutaneous fibers display different excitability properties to slowly increasing ramp pulses. Journal of neurophysiology 16 32783585
2019 Membrane-Protein Unfolding Intermediates Detected with Enhanced Precision Using a Zigzag Force Ramp. Biophysical journal 16 31882249
2018 Evolution of Diabetes Care in Hong Kong: From the Hong Kong Diabetes Register to JADE-PEARL Program to RAMP and PEP Program. Endocrinology and metabolism (Seoul, Korea) 16 29589385
2009 Phosphorylation of the SSBP2 and ABL proteins by the ZNF198-FGFR1 fusion kinase seen in atypical myeloproliferative disorders as revealed by phosphopeptide-specific MS. Proteomics 16 19658100
2002 Functional interaction of G protein-coupled receptors of the adrenomedullin peptide family with accessory receptor-activity-modifying proteins (RAMP). Microscopy research and technique 16 11921352
2020 The Chromatin Regulator ZMYM2 Restricts Human Pluripotent Stem Cell Growth and Is Essential for Teratoma Formation. Stem cell reports 15 32559458
2017 Temporal Regulation of fim Genes in Uropathogenic Escherichia coli during Infection of the Murine Urinary Tract. Journal of pathogens 15 29445547
2016 How to Properly Measure a Current-Voltage Relation?-Interpolation vs. Ramp Methods Applied to Studies of GABAA Receptors. Frontiers in cellular neuroscience 15 26869882
1991 Expression of Bordetella pertussis fimbrial (fim) genes in Bordetella bronchiseptica: fimX is expressed at a low level and vir-regulated. Microbial pathogenesis 15 1684407
2023 In Vitro Evolution to Increase the Titers of Difficult Bacteriophages: RAMP-UP Protocol. PHAGE (New Rochelle, N.Y.) 14 37350994